Robert Pless

Understanding vaccine safety information from the Vaccine Adverse Event Reporting System

The Vaccine Adverse Event Reporting System (VAERS) is administered by the Food and Drug Administration and CDC and is a key component of postlicensure vaccine safety surveillance. Its primary function is to detect early warning signals and generate hypotheses about possible new vaccine adverse events or changes in frequency of known ones. VAERS is a passive surveillance system that relies on physicians and others to voluntarily submit reports of illness after vaccination. Manufacturers are required to report all adverse events of which they become aware. There are a number of well-described limitations of such reporting systems. These include, for example, variability in report quality, biased reporting, underreporting and the inability to determine whether a vaccine caused the adverse event in any individual report. Strengths of VAERS are that it is national in scope and timely. The information in VAERS reports is not necessarily complete nor is it verified systematically. Reports are classified as serious or nonserious based on regulatory criteria. Reports are coded by VAERS in a uniform way with a limited number of terms using a terminology called COSTART. Coding is useful for search purposes but is necessarily imprecise. VAERS is useful in detecting adverse events related to vaccines and most recently was used for enhanced reporting of adverse events in the national smallpox immunization campaign. VAERS data have always been publicly available. However, it is essential for users of VAERS data to be fully aware of the strengths and weaknesses of the system. VAERS data contain strong biases. Incidence rates and relative risks of specific adverse events cannot be calculated. Statistical significance tests and confidence intervals should be used with great caution and not routinely. Signals detected in VAERS should be subjected to further clinical and descriptive epidemiologic analysis. Confirmation in a controlled study is usually required. An understanding of the systems defined objectives and inherent drawbacks is vital to the effective use of VAERS data in vaccine safety investigations.

Challenges and controversies in immunization safety.

No vaccine is perfectly safe or effective. As diseases such as diphtheria and polio fade, vaccine safety concerns, especially alleged links between vaccinations and several chronic illnesses, have become increasingly prominent in the media and to the public. This article reviews the current scientific evidence on several recent vaccine safety controversies. It also provides information on how various safety research is conducted, some of the concurrent challenges, and finally, some guidance on communicating with patients on vaccine risks.

Guidelines for collection, analysis and presentation of vaccine safety data in pre-and post-licensure clinical studies

Jan Bonhoeffer, Adwoa Bentsi-Enchill, Robert T. Chen, Margaret C. Fisher, Michael S. Gold, Katharina Hartman, Ulrich Heininger, Bernard Hoet, Thomas Jefferson, Najwa Khuri-Bulos, Katrin S. Kohl, S. Michael Marcy, David Nalin, Robert Pless, Hernan Sanabria-Rojas, Karen Sleeman, Robert Wise and The Brighton Collaboration Methods Working Group

Guidelines for collection, analysis and presentation of vaccine safety data in surveillance systems

Jan Bonhoeffer, Adwoa Bentsi-Enchill, Robert T. Chen, Margaret C. Fisher, Michael S. Gold, Katharina Hartman, Ulrich Heininger, Bernard Hoet, Thomas Jefferson, Najwa Khuri-Bulos, Katrin Kohl, S. Michael Marcy, David Nalin, Robert Pless, Hernan Sanabria-Rojas, Karen Sleeman, Robert Wise and The Brighton Collaboration Methods Working Group

Monitoring Vaccine Safety during Measles Mass Immunization Campaigns: Clinical and Programmatic Issues

In the planning and implementation of mass immunization campaigns, vaccine delivery has always been a priority. However, safety issues have gained increasingly more attention and grown in importance, and campaign planners must now take them into prime consideration. The World Health Organization has released guidelines to assist with the design and implementation of safety surveillance systems, primarily for developing countries, and these include a new monograph for measles mass campaigns. Experience in the past decade with mass campaigns (primarily in developed countries) shows that measles vaccine performs in these settings as anticipated from pre- and post-licensure studies. Serious adverse events are rare, even under the increased scrutiny extended during a campaign. The experience in developing country settings is growing. The implementation of safety surveillance for mass campaigns offers a unique opportunity for countries to avoid crisis situations and to begin vaccine safety monitoring in routine immunization programs.